Administration of recombinant human erythropoietin (rhEpo) stimulates erythropoiesis and increases red Dlood cell half-life, resulting in an increased hematocrit and potentially reducing the need for allogeneic blood transfusions in the critically ill patient. The original impetus for this project was to be able to control for these ystemic effects of rhEpo administration when examining the effects of rhEpo on cerebrovascular dysfunction in PROJECT 1. However, these effects on the occurrence and severity of anemia and on the need for blood transfusions may actually have equal or greater importance for long-term outcome than the neuroprotective effects. Patients with severe traumatic brain injury (TBI), like all critically ill patients, commonly develop anemia during the acute recovery period. Anemia after severe trauma is the result of a complex interaction of Dleeding, blunted Epo response to low hemoglobin concentrations, inflammatory mediators, and a hypoferremic state. Anemia requires the injured brain to maintain a higher cerebral blood flow (CBF) to maintain the same level of oxygen delivery. Cerebrovascular dysfunction caused by the trauma may prevent an adequate increase in CBF, which is the normal compensatory mechanism for a reduced oxygen-carrying capacity. Even if CBF does increase to maintain cerebral oxygen delivery, the resulting cerebral vasodilatation required to achieve the increase in CBF may result in an increased intracranial pressure (ICP). To optimize cerebral oxygenation in critically ill brain-injured patients, it is commonly recommended that hemoglobin concentration be maintained at approximately 10 g/dl. However, there is very little evidence that this practice actually improves cerebral hemodynamics or oxygenation, and maintaining hematocrit at this level commonly requires transfusion of blood products which may have significant risk. Trauma is the most common cause of death in the 1-44 yr age group, and the third most common cause for the entire US population. Trauma accounts for more loss of work life-years than cancer and cardiovascular diseases combined. Effective treatments for this important public health disorder are needed. We propose to study the role that erythropoietin administration might play in maintaining cerebral oxygenation after TBI. The specific aims include the following: 1-To study the role of anemia of critical illness on brain oxygenation and cerebral hemodynamics (including ICP) after TBI. 2-To study the complications associated with transfusion of blood products in patients with TBI. 3-To study the role of rhEpo administration on reducing the need for blood transfusion after TBI.